1. Field of Invention
This invention relates to a pharmaceutical method and composition for reducing intraocular pressure in living animals usually resulting from glaucoma using a wide range of organic sulfamates as active agents.
Glaucoma, a condition, wherein the intraocular pressure is elevated, may cause damage to the optic nerve and eventual blindness if not corrected.
The compounds generally may be administered orally, parenterally or topically to the eye as suspensions or when sufficiently soluble as solutions.
2. Information Disclosure Statement
Carbonic anhydrase enzyme which plays a part in reversibly catalyzing hydration of carbon dioxide in animals is at least in part responsible for aqueous humor formation in the eye and it is known that inhibitors of this enzyme can be used to relieve excessive eye pressure associated with glaucoma [Havener, Ocular Pharmacology, 4th Ed. (1978, C. V. Moseby); Maren, Investigative Ophthalmology, Vol. 13, pp. 479-484 (1974); Becker, Am. J. of Ophthalmology, Vol. 39, p. 177 (1955)].
U.S. Pat. No. 4,619,939 (Maren, T. H.) discloses the optical application to the eye of certain sulfonamides having carbonic anhydrase inhibition, water solubility of about 0.1% at pH 8.2 and first order rate penetration through a living rabbit cornea and other properties for the purpose of reducing aqueous humor formation and in intraocular pressure.
In contrast to the compounds of the Maren patent, the compounds of the present invention are sulfamates which differ structurally by incorporation of an oxygen atom which is interposed between the sulfonamide radical and the molecular moiety which carries the sulfamate group. More than one sulfamate group may be present. The use of the compounds of the present invention is not limited to topical application and therefore useful compounds are not confined to parameters suitable therefor. Many of the sulfamate compounds useful in the present invention are potent carbonic anhydrase inhibitors.
U.S. Pat. Nos. 4,513,006 and 4,582,916 disclose alicyclic compounds having a single sulfamate radical of the formula: ##STR1## having antiglaucoma activity wherein X is O or CH.sub.2 ; R.sup.1 is hydrogen or loweralkyl ; R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are hydrogen or loweralkyl and when X is CH.sub.2, R.sup.4 and R.sup.5 may be alkene groups joined to form a benzene ring and when X is oxygen, R.sup.2 and R.sup.3 and R.sup.4 and R.sup.5 together may form a methylenedioxy groups such as a sugar skeleton.
U.S. Pat. No. 4,591,601 disclosed dioxolane methane sulfamates to be useful as antiglaucoma agents.
U.S. Pat. No. 4,792,569 disclosed phenylethyl sulfamates to be useful as antiglaucoma agents having the formula: ##STR2## wherein R is alkyl, halo, alkoxy, trifluoromethyl or nitro and x is 0-3.
The compounds useful in the present invention are the subject of a commonly owned invention in application Ser. No. 365,212 filed on Jun. 12, 1989 wherein use in treating arthritis and osteoporosis is disclosed.